Women's Hospital, Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Women's Hospital, Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Hangzhou, Zhejiang, China.
Cell Rep. 2023 Apr 25;42(4):112351. doi: 10.1016/j.celrep.2023.112351. Epub 2023 Apr 4.
Much progress has been made toward generating analogs of early embryos, such as gastruloids and embryoids, in vitro. However, methods for how to fully mimic the cell movements of gastrulation and coordinate germ-layer patterning to induce head formation are still lacking. Here, we show that a regional Nodal gradient applied to zebrafish animal pole explant can generate a structure that recapitulates the key cell movements of gastrulation. Using single-cell transcriptome and in situ hybridization analysis, we assess the dynamics of the cell fates and patterning of this structure. The mesendoderm differentiates into the anterior endoderm, prechordal plate, notochord, and tailbud-like cells along an anterior-posterior axis, and an anterior-posterior-patterned head-like structure (HLS) progressively forms during late gastrulation. Among 105 immediate Nodal targets, 14 genes contain axis-induction ability, and 5 of them induce a complete or partial head structure when overexpressed in the ventral side of zebrafish embryos.
在体外生成早期胚胎类似物（如囊胚和类胚体）方面已经取得了很大进展。然而，如何完全模拟原肠胚形成的细胞运动并协调胚层模式形成以诱导头部形成的方法仍然缺乏。在这里，我们表明，应用于斑马鱼动物极外植体的局部 Nodal 梯度可以产生一种结构，该结构再现了原肠胚形成的关键细胞运动。通过单细胞转录组和原位杂交分析，我们评估了该结构的细胞命运和模式形成的动态。中胚层和内胚层沿着前后轴分化为前内胚层、前脊索板、脊索和尾芽样细胞，并且在晚期原肠胚形成过程中逐渐形成具有前后模式的头部样结构 (HLS)。在 105 个即时 Nodal 靶标中，有 14 个基因包含轴诱导能力，其中 5 个基因在斑马鱼胚胎的腹侧过表达时诱导完整或部分头部结构。
